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3,28-DISUBSTITUTED BETULINIC ACID DERIVATIVES AS ANTI-HIV AGENTS

Compounds according to Formula (I) are described along with compositions containing the same and methods of use thereof for the treatment of viral infections.

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Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors

Sirtuins are NAD+-dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide-based inhibitors that interact with the NAD+ binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X-ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5. Small changes make the difference: Systematic investigation of the acyl substrate specificity of sitruin 5 uncovers its unique preference for succinyl and glutaryl residues. Depending on the chemical nature of introduced modifications, either high-affinity substrates or sirtuin 5 specific inhibitors could be obtained.

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PHTHALAZINONE DERIVATIVES

A compound of formula (I); or an isomer, salt, solvate, chemically protected form, or prodrug thereof, wherein A and B together represent an optionally substituted, fused aromatic ring; RL is a C5-7aryl group substituted in the meta position by the group R2, and optionally further substituted; wherein R2 is selected from formula (II) and formula (III); and its use as a pharmaceutical, in particular for the treatment of diseases ameliorated by inhibiting the activity of PARP

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Diacylglycerol Acyltransferase Inhibitors

Provided herein are compounds of the formula (I): were R1 is phenyl, R2 is hydrogen, halogen or lower alkyl, X is carbon on nitrogen, and R3 is isoquinoline, -amino, or a 4- to 6-membered heterocycloalkyl ring and pharmaceutically acceptable salts thereof, which are active as DGAT inhibitors and therefore find uses in treatment of diseases associated with abnormal metabolism of triglicerides such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

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Spirocyclic oxetanes: Synthesis and properties

(Chemical Presented) Wormholes through chemical space: Spirocyclic oxetanes are described as analogues of morpholine and also as topological siblings of their carbonyl counterparts. They are particularly promising in terms of both their physicochemical properties and the ease with which they can be grafted onto molecular structures. The data collected highlight oxetanes as both the hydrophilic sister of a gem-dimethyl unit and the carbonyl group’s lipophilic brother.

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Related Products of 17347-61-4, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 17347-61-4, molcular formula is C6H8O3, introducing its new discovery.

Meta-anilide and meta-anilide urea and urea salt herbicidal compounds and methods of use

A compound having the structural formula STR1 wherein R is selected from the group consisting of hydrogen and C1 -C3 alkyl ammonium; R’ is selected from the group consisting of C2 -C8 alkyl, C1 -C3 alkoxy, cyclopropyl, methacryl, C1 -C3 alkylmercapto, methylamino, ethylamino, C2 -C4 dialkylamino, C2 -C4 alkylalkoxyamino; and n equals the integer 0 or 1; and its use as a herbicide and as a herbicide intermediate.

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Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity

In this study, 12 known cycloartane triterpenoids (1?12) with four different skeletons isolated from the roots of Souliea vaginata were screened for the first time for in vitro anti-HIV activity using AZT as a standard. Among the compounds, beesioside I (1) showed the highest potency against HIV-1NL4-3 with an EC50 value of 2.32 muM (CC50 > 40 muM). Preliminary structure-activity relationship (SAR) studies on 1 indicated that simple modification of its aglycone (13) could significantly influence the antiviral activity. Particularly, the introduction of an acyl group at the C-3 position of 13 led to significant improvement in both anti-HIV potency and selectivity index. Among all synthetically modified derivatives, compound 13g was the most potent compound with an EC50 value of 0.025 muM and TI value greater than 800, comparable to those of 3-O-(3?,3?-dimethylsuccinyl)-betulinic acid (DSB, bevirimat). Other analogues exhibited strong to weak inhibition of HIV-1 replication in MT-4 cells. The length, carboxylic terminus, and C-3? dimethyl substitution of the C-3 side chain substantially affected the anti-HIV activity. Finally, compound 13g was an effective agent against HIV with high potential for further investigation.

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Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolytic principle

The neotropical lianas Souroubea gilgii and Souroubea sympetala (Marcgraviaceae) were chosen for study as part of a phytochemical discovery strategy focusing on rare plant families in Central America. In participatory research, Q’eqchi’ healers in Belize reported the use of these plants to reverse psychological symptoms inflicted by witchcraft. Extracts of two Souroubea species showed significant anti-anxiety activity in the elevated plus maze, a standardized test paradigm. Bioassay guided isolation led to the active principle, the pentacyclic triterpene, betulinic acid, which had activity in the elevated plus maze at 0.5 mg/kg. Other phytochemicals isolated included alpha- and beta-amyrin, 2-hydroxyursolic acid, taraxenyl trans-4-hydroxy-cinnamate, naringenin, methyl ursolate, eriodytiol, methyl 2-alpha-hydroxyursolate, methyl 2-alpha-hydroxymaslinate, methyl betulinate, and condrilla sterol.

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Proton grease: An acid accelerated molecular rotor

A molecular rotor was designed that rotates 7 orders of magnitude faster upon protonation. The quinoline rotor is based on a rigid N-arylimide framework that displays restricted rotation due to steric interaction between the quinoline nitrogen and imide carbonyls. At rt (23 C), the rotor rotates slowly (t1/2 = 26 min, DeltaG? = 22.2 kcal/mol). However, upon addition of 3.5 equiv of acid the rotor rotates rapidly (t 1/2 = 2.0 ¡Á 10-4 s, DeltaG? = 12.9 kcal/mol). Mechanistic studies show that this dramatic acid catalyzed change is due to stabilization of the planar transition state by the formation of an intramolecular hydrogen bond between the protonated quinoline nitrogen (N+-H) and an imide carbonyl (O=C). The acid catalyzed acceleration is reversible and can be stopped by addition of base.

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Ashless additives for lubricating compositions

Superior ashless additives for lubricants are prepared by a process comprising first introducing a petroleum sulfonic acid and a polyamine to a reaction zone and subsequently introducing a cyclic anhydride of a dicarboxylic acid into the reaction zone. In another embodiment, the solids content of the additives is reduced to acceptable levels by removal of free SO2 from the petroleum sulfonic acid prior to preparing the additive. Lubricating oil compositions containing these ashless additives are also provided.

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